title: Analysis of 6 single-nucleotide polymorphisms in the androgen receptor gene in Chilean patients with primary spermatogenic failure.
abstract: Androgens are essential for spermatogenesis. It has been postulated that  androgen activity is modulated directly or indirectly by genetic variability  in the androgen receptor gene sequence, including CAG/GGN polymorphisms and  single-nucleotide polymorphisms (SNP). In this study, the frequency of 6 SNPs  that constitute a haplotype in the androgen receptor sequence was determined  by enzyme restriction assays and allele-specific polymerase chain reactions in  117 secretory azo/oligozoospermic men (93 idiopathic and 24 excryptorchidic),  and in 121 controls with normal spermatogenesis (42 obstructive and 79  normozoospermic men) whose hormonal measurements and length of CAG/GGN  polymorphisms were previously determined. The frequency of these 6 SNPs was  not different between patients and controls. A total of 10 haplotypes (HAPs  1-10) formed by these 6 SNPs were found, and one of these haplotypes was  observed with high frequency in the total population (HAP1, 83.2%; P  < .001, χ(2) test). The frequency of the 10 haplotypes was not  different between patients and controls, except for HAP5, which was only  detected in one patient with a history of bilateral cryptorchidism (P  = 0.014, Bonferroni test). On the other hand, no associations were found  between the haplotypes studied and shorter or longer CAG or GGN polymorphisms.  Interestingly, we found that the CAG 21 allele, which was previously  correlated with an increased risk of idiopathic spermatogenic impairment, was  more frequently found among the less common haplotypes that have higher  follicle-stimulating hormone serum levels. In summary, we did not find an  increased frequency of particular haplotypes in infertile men with idiopathic  spermatogenic impairment compared with control men; however, we found that the  CAG 21 allele, which appears to be associated with male infertility, is  observed at a significantly higher proportion among the less common androgen  receptor haplotypes.
authors.affiliation: Institute of Maternal and Child Research, School of Medicine, University of Chile, Santa Rosa 1234, Santiago, Chile.
authors.forename: Alexis
authors.initials: A
authors.lastname: Parada-Bustamante
authors.forename: María Cecilia
authors.initials: MC
authors.lastname: Lardone
authors.forename: Raúl
authors.initials: R
authors.lastname: Valdevenito
authors.forename: Mauricio
authors.initials: M
authors.lastname: Ebensperger
authors.forename: Patricia V
authors.initials: PV
authors.lastname: López
authors.forename: Marcia
authors.initials: M
authors.lastname: Madariaga
authors.forename: Antonio
authors.initials: A
authors.lastname: Piottante
authors.forename: Andrea
authors.initials: A
authors.lastname: Castro
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D002677:Chile; D017931:DNA Primers; D006239:Haplotypes; D006801:Humans; D007248:Infertility, Male / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011944:Receptors, Androgen / Q000235:genetics*; D013091:Spermatogenesis
chemical_list: D017931:DNA Primers; D011944:Receptors, Androgen